Carbon nanotubes (CNTs) are widely used in the aerospace, automotive, and electronics industries because of their stability, enhanced metallic, and electrical properties. CNTs are also being investigated for biomedical applications such as drug delivery systems and biosensors. However, the toxic potential of CNTs was reported in various cell lines and animal models. The toxicity depends on diverse properties of the CNTs, such as length, aspect ratio, surface area, degree of aggregation, purity, concentration, and dose. In addition, CNTs and/or associated contaminants were well known for oxidative stress, inflammation, apoptosis, pulmonary inflammation, fibrosis, and granuloma in lungs. The increased production of CNTs likely enhanced the possibility of its exposure in people. Studies on the toxicity of CNTs are mainly focused on the pulmonary effects after intratracheal administration, and only a few studies are reported about the toxicity of CNTs via other routes of exposure. So, it is essential to consider the chronic toxicity of CNTs before using them for various biomedical applications. This review focuses on the potential toxicities of CNTs.
Polymannose (PM) having a weight-average molar mass (M) of 30-53 kDa was synthesized by the polycondensation of mannose using phosphorous acid as the catalyst and characterized by various techniques such as NMR, IR, GPC and polarimetry. 2D NMR results confirmed the presence of (1 → 6)-linked α-D-mannose residues as backbone with O-3 and O-2 substituted linear or branched chains in PM. Amphotericin B (AmB) was conjugated to periodate-oxidized PM through Schiff's linkages at 20 wt% concentration. The AmB-PM conjugates were highly soluble in phosphate buffered saline (180-250 mg/mL), exhibited negligible hemolytic potential to human erythrocytes even at a concentration of 200 μg/mL (equivalent to ~40 μg/mL AmB) and were non-toxic to human embryonic kidney (HEK293T) cells even at a concentration of 250 μg/mL (equivalent to ~50 μg/mL AmB). The minimum inhibitory concentration of the AmB-PM conjugates against C. albicans, C. parapsilosis and C. neoformans was in the range of 0.5-1.0 μg/mL. Mannose receptors are widely expressed on myeloid cells such as macrophages, neutrophils, and dendritic cells. Therefore, apart from treating fungal infections, AmB-PM conjugates also may have therapeutic potential for the treatment of macrophage-associated diseases such as leishmaniasis where mannose receptors are overexpressed.
Laryngeal carcinoma, the most common among head and neck squamous cell carcinoma (HNSCC) induces 1% of all cancer deaths. Curcumin, the active constituent of turmeric is more effective in the treatment of various cancer. In the present study, with an aim to explore the mechanistic role of BDMC-A as a chemotherapeutic agent, we have investigated the inhibitory effect of BDMC-A on invasion, angiogenesis, and metastasis in Hep-2 cells and compared it with curcumin. Curcumin and BDMC-A treated Hep-2 cells were quanti ed using western blotting and RT-PCR technique to investigate the effect of Curcumin and BDMC-A on transcription factors involved in signal transduction cascade, invasion and angiogenesis associated markers. Pro-in ammatory markers of curcumin and BDMC-A treated Hep-2 cells were estimated using the ELISA kit. The results showed that BDMC-A might exhibit the anti-cancer activity by inhibiting transcription factors mainly NF-κB, p65, c-Jun, c-Fos, STAT3, 5, PPAR-γ and βcatenin, which are responsible for tumor progression and malignancy. Downregulation of MMP-9, VEGF, IL-6 and IL-8 and upregulation of TIMP-2 levels further supports the anti-tumor potential of BDMC-A. Our overall results revealed that BDMC-A more effectively inhibited the markers of invasion, angiogenesis and metastasis in comparison with curcumin.
Cancer is one of the most widespread deadly diseases, following cardiovascular disease, worldwide. Chemotherapy is widely used in combination with surgery, hormone and radiation therapy to treat various cancers. However, chemotherapeutic drugs can cause severe side effects due to non-specific targeting, poor bioavailability, low therapeutic indices, and high dose requirements. Several drug carriers successfully overcome these issues and deliver drugs to the desired sites, reducing the side effects. Among various drug delivery systems, polysaccharide-based carriers that target only the cancer cells have been developed to overcome the toxicity of chemotherapeutics. Polysaccharides are non-toxic, biodegradable, hydrophilic biopolymers that can be easily modified chemically to improve the bioavailability and stability for delivering therapeutics into cancer tissues. Different polysaccharides, such as chitosan, alginates, cyclodextrin, pullulan, hyaluronic acid, dextran, guar gum, pectin, and cellulose, have been used in anti-cancer drug delivery systems. This review highlights the recent progress made in polysaccharides-based drug carriers in anti-cancer therapy.
We have investigated the time-dependent effect of multi-walled carbon nanotubes (MWCNTs) in rats upon single inhalation exposure followed by intermittent sacrifice. The effects were monitored by analyzing the bronchoalveolar lavage fluid (BALF) and histopathological analysis. Cell count, neutrophils, lymphocytes, lactate dehydrogenase, alkaline phosphatase, protein and cytokines (tumor necrosis factor-alpha (TNF-α) and interleukin 4 (IL-4)) were significantly increased, while cell viability and alveolar macrophage count significantly decreased in the BALF of MWCNT-treated rats on day 1, day 7 and day 14 post-exposure, when compared to control rats. Histopathological analysis revealed inflammation, fibrosis and granuloma in the lungs of MWCNTs-treated rats on day 7 and day 14 post-exposure. We interpret that MWCNT induces inflammation, fibrosis and granuloma characterized by progressive elevation of TNF-α and IL-4. Histopathological studies further support our view and reveal the distribution of MWCNT in lungs and tracheobronchial lymph nodes (TBLN). We conclude that MWCNT-induced pulmonary toxicity is considerable even on single exposure.
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